Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study.

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Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_903C24CD6C23
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study.
Journal
Annals of oncology
Author(s)
Gadgeel S., Peters S., Mok T., Shaw A.T., Kim D.W., Ou S.I., Pérol M., Wrona A., Novello S., Rosell R., Zeaiter A., Liu T., Nüesch E., Balas B., Camidge D.R.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Publication state
Published
Issued date
01/11/2018
Peer-reviewed
Oui
Volume
29
Number
11
Pages
2214-2222
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX.
Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression.
In total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib, n = 64; crizotinib, n = 58), 43 had measurable lesions (alectinib, n = 21; crizotinib, n = 22), and 46 had received prior radiotherapy (alectinib, n = 25; crizotinib, n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25-0.64] and those without (HR 0.51, 95% CI: 0.33-0.80, P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not.
Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advanced ALK+ NSCLC, irrespective of prior CNS disease or radiotherapy.
ClinicalTrials.gov NCT02075840.
Keywords
Adult, Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase/antagonists & inhibitors, Anaplastic Lymphoma Kinase/genetics, Brain/diagnostic imaging, Brain/drug effects, Brain/radiation effects, Brain Neoplasms/diagnostic imaging, Brain Neoplasms/genetics, Brain Neoplasms/secondary, Brain Neoplasms/therapy, Carbazoles/pharmacology, Carbazoles/therapeutic use, Carcinoma, Non-Small-Cell Lung/diagnostic imaging, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/secondary, Carcinoma, Non-Small-Cell Lung/therapy, Chemoradiotherapy/methods, Crizotinib/pharmacology, Crizotinib/therapeutic use, Disease Progression, Female, Humans, Lung/diagnostic imaging, Lung/drug effects, Lung/radiation effects, Lung Neoplasms/diagnostic imaging, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Lung Neoplasms/therapy, Magnetic Resonance Imaging, Male, Middle Aged, Piperidines/pharmacology, Piperidines/therapeutic use, Treatment Outcome, Tumor Burden/drug effects, Tumor Burden/radiation effects, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
19/09/2018 10:09
Last modification date
16/11/2019 7:16
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